Research Article

Cryptic genetic variation accelerates evolution by opening access to diverse adaptive peaks

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Science  26 Jul 2019:
Vol. 365, Issue 6451, pp. 347-353
DOI: 10.1126/science.aax1837

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Cryptic alleles make a bridge for adaptation

Protein function is generally constrained by selective parameters that can inhibit evolutionary potential. It has thus been difficult to determine how novelties arise. Zheng et al. allowed bacterial populations to accumulate mutations and then used directed evolution to evolve green fluorescent protein function from a gene that expressed yellow fluorescent protein (see the Perspective by Lee and Marx). Protein alternatives could evolve in cases where cryptic alleles—selectively neutral or mildly deleterious genetic variants with no apparent phenotypic differences—were present in the population. Thus, cryptic alleles provide an evolutionary bridge between diversity and selection and facilitate the generation of novel adaptations.

Science, this issue p. 347; see also p. 318


Cryptic genetic variation can facilitate adaptation in evolving populations. To elucidate the underlying genetic mechanisms, we used directed evolution in Escherichia coli to accumulate variation in populations of yellow fluorescent proteins and then evolved these proteins toward the new phenotype of green fluorescence. Populations with cryptic variation evolved adaptive genotypes with greater diversity and higher fitness than populations without cryptic variation, which converged on similar genotypes. Populations with cryptic variation accumulated neutral or deleterious mutations that break the constraints on the order in which adaptive mutations arise. In doing so, cryptic variation opens paths to adaptive genotypes, creates historical contingency, and reduces the predictability of evolution by allowing different replicate populations to climb different adaptive peaks and explore otherwise-inaccessible regions of an adaptive landscape.

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